Trial Outcomes & Findings for Prospective Validation of a Plasma Transfusion Dosing Algorithm in Patients With Chronic Liver Disease (NCT NCT02366845)

Last Updated: 2019-10-29

Results Overview

Ability of dosing algorithm to accurately predict necessary plasma dose (ml/kg), required to reach commonly targeted International Normalized Ratio (INR) values, compared to clinician chosen plasma transfusion dose, as determined by dose-response curve. The primary outcome was achievement of the target INR within ±0.1 after the first round of FFP transfusion. This primary outcome was selected because underdosing can result in prolonged bleeding, delayed procedure times, and more rounds of FFP transfusion. Furthermore, overdosing can result in excess cost, increased portal pressures, bleeding, transfusion associated circulatory overload (TACO), and transfusion related acute lung injury (TRALI).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

50 participants

Primary outcome timeframe

within 1 hour after entire plasma transfusion

Results posted on

2019-10-29

Participant Flow

Participant milestones

Participant milestones
Measure	Clinician Chosen Dosing University of Colorado Hospital or Denver Health bleeding inpatients with chronic liver disease receiving fresh frozen plasma (FFP) for clinical indications as determined by hospital clinician. Total dose determined by physician. (Current standard of care). Physician chosen dose will be utilized but physician blinded to which dosing strategy used. INR measurement performed within 1 hour after total transfusion of plasma. No other transfused blood component, crystalloid or colloidal fluid infused between the first and second INR studies except plasma Fresh Frozen Plasma: An INR dose-response curve with associated transfusion algorithm was generated for plasma in bleeding patients with chronic liver disease. In the intervention arm we will determine the plasma transfusion dose using the algorithm dosing table based on the pre-transfusion INR and the clinician chosen INR target. In the usual care group the dosing will be determined by the clinician.	Algorithm Dosing University of Colorado Hospital or Denver Health bleeding inpatients with chronic liver disease receiving fresh frozen plasma (FFP) for clinical indications as determined by hospital clinician. This group received plasma doses based on study dosing algorithm table. Pre-transfusion INR, target post-transfusion INR, and study table used to determine FFP dose in (ml/kg). INR measurement performed within 1 hour after entire FFP transfusion administered. No other transfused blood component,crystalloid or colloidal fluid infused between first and second INR studies except plasma. Fresh Frozen Plasma: An INR dose-response curve with associated transfusion algorithm was generated for plasma in bleeding patients with chronic liver disease. In the intervention arm we will determine the plasma transfusion dose using the algorithm dosing table based on the pre-transfusion INR and the clinician chosen INR target. In the usual care group the dosing will be determined by the clinician.
Overall Study STARTED	25	25
Overall Study COMPLETED	25	25
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Prospective Validation of a Plasma Transfusion Dosing Algorithm in Patients With Chronic Liver Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Clinician Chosen Dosing n=24 Participants Usual Care arm: Physician determined fresh frozen plasma (FFP) dosing. Bleeding patients admitted to study hospitals,with chronic liver disease determined to receive fresh frozen plasma (FFP) for clinical indications as determined by hospital clinician. Total dose determined by physician's judgment (current standard of care). Physician chosen dose will be utilized but physician will be unaware of which dosing strategy utilized. International Normalized Ratio (INR) measurement will be performed within 1 hour after entire plasma transfusion administered. No other transfused blood component, crystalloid or colloidal fluid infused between first and second INR studies except plasma.	Algorithm Dosing n=26 Participants Intervention arm: Plasma transfusion dose determined using algorithm dosing table based on the (pre-transfusion INR) and clinician chosen INR target. Bleeding patients admitted to study hospitals with chronic liver disease determined to receive fresh frozen plasma (FFP) for clinical indications as determined by hospital clinician. Pre-transfusion INR and target post-transfusion INR used to determine FFP dose. The study table determines dose in (ml/kg) of FFP. INR measurement will be performed within 1 hour after entire plasma transfusion administered. No other transfused blood component,crystalloid or colloidal fluid will be infused between the first and second INR studies except plasma.	Total n=50 Participants Total of all reporting groups
Age, Continuous	53.7 years STANDARD_DEVIATION 11.1 • n=5 Participants	53.3 years STANDARD_DEVIATION 10.7 • n=7 Participants	53.5 years STANDARD_DEVIATION 10.8 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	16 Participants n=7 Participants	31 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	13 participants n=5 Participants	16 participants n=7 Participants	29 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	9 participants n=5 Participants	8 participants n=7 Participants	17 participants n=5 Participants
Race/Ethnicity, Customized Asian	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Pre-Transfusion International Normalzied Ratio (INR)	2.4 ratio STANDARD_DEVIATION 0.5 • n=5 Participants	2.3 ratio STANDARD_DEVIATION 0.4 • n=7 Participants	2.3 ratio STANDARD_DEVIATION 0.5 • n=5 Participants
Physician target International Normalized Ratio (INR)	1.7 ratio STANDARD_DEVIATION 0.2 • n=5 Participants	1.8 ratio STANDARD_DEVIATION 0.2 • n=7 Participants	1.7 ratio STANDARD_DEVIATION 0.2 • n=5 Participants
Hospital Service Medical Floor	23 participants n=5 Participants	22 participants n=7 Participants	45 participants n=5 Participants
Hospital Service Other	1 participants n=5 Participants	4 participants n=7 Participants	5 participants n=5 Participants
Serum Creatinine	1.3 mg/dL n=5 Participants	1.2 mg/dL n=7 Participants	1.3 mg/dL n=5 Participants
APACHE II Score	13.9 units on a scale STANDARD_DEVIATION 6.7 • n=5 Participants	13.9 units on a scale STANDARD_DEVIATION 3.5 • n=7 Participants	13.9 units on a scale STANDARD_DEVIATION 5.3 • n=5 Participants
MELD Score	25.9 units on a scale STANDARD_DEVIATION 8.4 • n=5 Participants	25.4 units on a scale STANDARD_DEVIATION 5.4 • n=7 Participants	25.6 units on a scale STANDARD_DEVIATION 7.0 • n=5 Participants

PRIMARY outcome

Timeframe: within 1 hour after entire plasma transfusion

Population: At goal INR after first transfusion.

Outcome measures

Outcome measures
Measure	Clinician Chosen Dosing n=24 Participants Usual Care arm: Physician determined FFP dosing. Bleeding patients admitted to study hospitals,with chronic liver disease determined to receive fresh frozen plasma (FFP) for clinical indications as determined by hospital clinician. Total dose determined by physician's judgment (current standard of care). Physician chosen dose will be utilized but physician will be unaware of which dosing strategy utilized. INR measurement will be performed within 1 hour after entire plasma transfusion administered. No other transfused blood component, crystalloid or colloidal fluid infused between first and second INR studies except plasma	Algorithm Dosing n=26 Participants Intervention arm: Plasma transfusion dose determined using algorithm dosing table based on the pre-transfusion INR and clinician chosen INR target. Bleeding patients admitted to study hospitals with chronic liver disease determined to receive fresh frozen plasma (FFP) for clinical indications as determined by hospital clinician. Pre-transfusion INR and target post-transfusion INR used to determine FFP dose. The study table determines dose in (ml/kg) of FFP. INR measurement will be performed within 1 hour after entire plasma transfusion administered. No other transfused blood component,crystalloid or colloidal fluid will be infused between the first and second INR studies except plasma.
Number of Participants That Reached Targeted International Normalized Ratio (INR) Within ±0.1 After First Fresh Frozen Plasma (FFP) Transfusion Completed.	7 Participants	17 Participants

SECONDARY outcome

Timeframe: hours from first dose to initiation of procedure, anticipated timeframe between 1 minute to 8 hours.

Decreased time between initiation of plasma infusion, achieving a corrected target INR and start of planned patient procedures would potentially improve care efficiency and/or allow faster intervention in unstable patients.

Outcome measures

Outcome measures
Measure	Clinician Chosen Dosing n=24 Participants Usual Care arm: Physician determined FFP dosing. Bleeding patients admitted to study hospitals,with chronic liver disease determined to receive fresh frozen plasma (FFP) for clinical indications as determined by hospital clinician. Total dose determined by physician's judgment (current standard of care). Physician chosen dose will be utilized but physician will be unaware of which dosing strategy utilized. INR measurement will be performed within 1 hour after entire plasma transfusion administered. No other transfused blood component, crystalloid or colloidal fluid infused between first and second INR studies except plasma	Algorithm Dosing n=26 Participants Intervention arm: Plasma transfusion dose determined using algorithm dosing table based on the pre-transfusion INR and clinician chosen INR target. Bleeding patients admitted to study hospitals with chronic liver disease determined to receive fresh frozen plasma (FFP) for clinical indications as determined by hospital clinician. Pre-transfusion INR and target post-transfusion INR used to determine FFP dose. The study table determines dose in (ml/kg) of FFP. INR measurement will be performed within 1 hour after entire plasma transfusion administered. No other transfused blood component,crystalloid or colloidal fluid will be infused between the first and second INR studies except plasma.
Time (Hours) From Initiation of First Dose of Plasma to Initiation of Planned Procedure (in Patient Undergoing Transfusion Before a Procedure) for Clinician Dosing Compared to Algorithm Dosing Strategies.	4.9 hours Interval 3.5 to 6.8	3.5 hours Interval 2.7 to 4.5

SECONDARY outcome

Timeframe: within 1 hour after entire plasma transfusion

Outcome measures

Outcome measures
Measure	Clinician Chosen Dosing n=24 Participants Usual Care arm: Physician determined FFP dosing. Bleeding patients admitted to study hospitals,with chronic liver disease determined to receive fresh frozen plasma (FFP) for clinical indications as determined by hospital clinician. Total dose determined by physician's judgment (current standard of care). Physician chosen dose will be utilized but physician will be unaware of which dosing strategy utilized. INR measurement will be performed within 1 hour after entire plasma transfusion administered. No other transfused blood component, crystalloid or colloidal fluid infused between first and second INR studies except plasma	Algorithm Dosing n=26 Participants Intervention arm: Plasma transfusion dose determined using algorithm dosing table based on the pre-transfusion INR and clinician chosen INR target. Bleeding patients admitted to study hospitals with chronic liver disease determined to receive fresh frozen plasma (FFP) for clinical indications as determined by hospital clinician. Pre-transfusion INR and target post-transfusion INR used to determine FFP dose. The study table determines dose in (ml/kg) of FFP. INR measurement will be performed within 1 hour after entire plasma transfusion administered. No other transfused blood component,crystalloid or colloidal fluid will be infused between the first and second INR studies except plasma.
Dose Difference (Average # Units) Between Clinician Dosing and Algorithm Dosing (Units of FFP) Per Patient.	2.4 units Interval 1.9 to 3.0	3.1 units Interval 2.5 to 3.9

SECONDARY outcome

Timeframe: Subjects will be followed for duration of hospital stay, anticipated within 1 Day to 28 Days

Outcome measures

Outcome measures
Measure	Clinician Chosen Dosing n=24 Participants Usual Care arm: Physician determined FFP dosing. Bleeding patients admitted to study hospitals,with chronic liver disease determined to receive fresh frozen plasma (FFP) for clinical indications as determined by hospital clinician. Total dose determined by physician's judgment (current standard of care). Physician chosen dose will be utilized but physician will be unaware of which dosing strategy utilized. INR measurement will be performed within 1 hour after entire plasma transfusion administered. No other transfused blood component, crystalloid or colloidal fluid infused between first and second INR studies except plasma	Algorithm Dosing n=26 Participants Intervention arm: Plasma transfusion dose determined using algorithm dosing table based on the pre-transfusion INR and clinician chosen INR target. Bleeding patients admitted to study hospitals with chronic liver disease determined to receive fresh frozen plasma (FFP) for clinical indications as determined by hospital clinician. Pre-transfusion INR and target post-transfusion INR used to determine FFP dose. The study table determines dose in (ml/kg) of FFP. INR measurement will be performed within 1 hour after entire plasma transfusion administered. No other transfused blood component,crystalloid or colloidal fluid will be infused between the first and second INR studies except plasma.
Hospital Length of Stay	13.8 days Interval 9.8 to 19.4	11.0 days Interval 7.0 to 17.2

Adverse Events

Clinician Chosen Dosing

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Algorithm Dosing

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Marc Moss

University of Colorado

Phone: 303-724-6080

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place